BACKGROUND: The opioid crisis and the hepatitis C virus epidemic perpetuate and potentiate each other in a syndemic with escalating morbidity. Policy-driven funding can help resolve the syndemic through collaborative solutions that rapidly translate evidence-based interventions into real-world applications.
METHODS: We report development and programmatic evaluation of Peer-Assisted Telemedicine for Hepatitis C (PATHS), which utilizes State Opioid Response (SOR) funding to scale-up a positive randomized trial of peer-assisted telemedicine HCV treatment. PATHS employs staff within an academic medical center and partners with people with lived experience of drug use, \"peers,\" to recruit rural-dwelling people who use drugs living with HCV. PATHS staff record patient data by abstracting clinical records or directly communicating with patients and peers. Peers are funded by a separate SOR-supported program administered through the state health authority. Peers support patients through HCV screening, treatment initiation via telemedicine, adherence, and cure.
RESULTS: Between March 2021 and June 2024, PATHS expanded to 18 of Oregon\'s 36 counties. In that time, PATHS diagnosed 198 rural PWUD with HCV. One hundred sixty-seven (84.3 %) linked to telemedicine and of these, 145 (86.8 %) initiated treatment. Of those who initiated treatment, 91 (62.8 %) completed treatment, of which 61 (67.0 %) are cured.
CONCLUSIONS: By rapidly translating a clinical innovation in HCV treatment to achieve highly effective real-world results, PATHS models how policy-driven funding can facilitate collaboration between community partners, academic medical centers, and state health departments to end the opioid-HCV syndemic.

Polysubstance use (PSU), injection drug use (IDU), and equipment sharing are associated with bloodborne infection (BBI) transmission risk, particularly Hepatitis C Virus (HCV), yet data on PSU in low- and middle-income countries (LMICs) is limited. We report on baseline PSU, medication-assisted treatment (MAT) engagement, and motivation to reduce IDU among 95 people who inject drugs (PWID) who accessed needle and syringe programs (NSP) in Nairobi and Coastal Kenya prior to HCV treatment. Bivariate and multivariate logistic regression were used to examine the associations between PSU and behaviors that confer HCV transmission and acquisition risks. Most participants (70.5%) reported PSU in the last 30 days, and one-third (35.8%) reported PSU exclusive to just heroin and cannabis use. Common combinations were heroin and cannabis (49.3%), and heroin, cannabis, and bugizi (flunitrazepam) (29.9%). Participants at baseline were receiving MAT (69.5%), already stopped or reduced IDU (30.5%), and were HIV-positive (40%). PSU was significantly associated with IDU (p = 0.008) and the number of times (p = 0.016) and days (p = 0.007) injected in the last 30 days. Participants reported high PSU and equipment sharing, despite high MAT engagement. While co-locating BBI treatment within existing harm reduction services is necessary to promote uptake and curb re-infection, tailored services may be needed to address PSU, particularly in LMICs.

The hepatitis C virus (HCV) co-opts many cellular factors-including proteins and microRNAs-to complete its life cycle. A cellular RNA-binding protein, poly(rC)-binding protein 2 (PCBP2), was previously shown to bind to the hepatitis C virus (HCV) genome; however, its precise role in the viral life cycle remained unclear. Herein, using the HCV cell culture (HCVcc) system and assays that isolate each step of the viral life cycle, we found that PCBP2 does not have a direct role in viral entry, translation, genome stability, or HCV RNA replication. Rather, our data suggest that PCBP2 depletion only impacts viral RNAs that can undergo genome packaging. Taken together, our data suggest that endogenous PCBP2 modulates the early steps of genome packaging, and therefore only has an indirect effect on viral translation and RNA replication, likely by increasing the translating/replicating pool of viral RNAs to the detriment of virion assembly.

The hepatitis C virus (HCV) is responsible for approximately 50 million infections worldwide. Effective drug treatments while available face access barriers, and vaccine development is hampered by viral hypervariability and immune evasion mechanisms. The CD4+ and CD8+ T-cell responses targeting HCV non-structural (NS) proteins have shown a role in the viral clearance. In this paper, we reviewed the studies exploring the relationship between HCV structural and NS proteins and their effects in contributing to the elicitation of an effective T-cell immune response. The use of different vaccine platforms, such as viral vectors and virus-like particles, underscores their versability and efficacy for vaccine development. Diverse HCV antigens demonstrated immunogenicity, eliciting a robust immune response, positioning them as promising vaccine candidates for protein/peptide-, DNA-, or RNA-based vaccines. Moreover, adjuvant selection plays a pivotal role in modulating the immune response. This review emphasizes the importance of HCV proteins and vaccination strategies in vaccine development. In particular, the NS proteins are the main focus, given their pivotal role in T-cell-mediated immunity and their sequence conservation, making them valuable vaccine targets.

UNASSIGNED: Therapeutic drug monitoring (TDM) can be a useful tool in the clinical management of anti-hepatitis C virus (anti-HCV) drugs. Methods for the determination of various types of anti-HCV drugs in biological samples are, therefore, needed for clinical laboratories.
UNASSIGNED: In this work, employing the LC-MS/MS approach, we aimed to develop a multiplexed method for identification of the following anti-HCV drugs: Ribavirin (RBV), Boceprevir (BOC), Telaprevir (TVR), Simeprevir (SIM), Daclatasvir (DAC), Sofosbuvir (SOF) and its metabolite GS 331007 (SOFM) in liquid plasma and in dried plasma spots (DPSs).
UNASSIGNED: A single-step extractive-deproteinization was employed for both liquid plasma and DPSs. Reverse-phase liquid chromatography coupled with MRM detection was developed for multiplexed drug detection and quantification.
UNASSIGNED: Sensitivities (expressed as LOQ) were 10 (±1.2), 10 (±4.9), 10 (±4.4), 10 (±4.4), 10 (±6.4), 10 (±3.4), 10 (±6.4) ng/ml for RBV, SOFM, SOF, DAC, BOC, TVR, and SIM, respectively; accuracy (expressed as BIAS%) was <10% for all drugs; reproducibility (intra- and inter-day CV%) was <10% for all drugs; dynamic range was 10-10,000 ng/ml for all drugs.
UNASSIGNED: A novel, simple, rapid and robust LC-MS/MS multiplex assay for the TDM of various anti-HCV drugs that are currently in the clinic was successfully developed. Application to DPS samples enabled TDM to be used for outpatients as well.

Addressing the complexities of managing viral infections during pregnancy is essential for informed medical decision-making. This comprehensive review delves into the management of key viral infections impacting pregnant women, namely Human Immunodeficiency Virus (HIV), Hepatitis B Virus/Hepatitis C Virus (HBV/HCV), Influenza, Cytomegalovirus (CMV), and SARS-CoV-2 (COVID-19). We evaluate the safety and efficacy profiles of antiviral treatments for each infection, while also exploring innovative avenues such as gene vaccines and their potential in mitigating viral threats during pregnancy. Additionally, the review examines strategies to overcome challenges, encompassing prophylactic and therapeutic vaccine research, regulatory considerations, and safety protocols. Utilizing advanced methodologies, including PBPK modeling, machine learning, artificial intelligence, and causal inference, we can amplify our comprehension and decision-making capabilities in this intricate domain. This narrative review aims to shed light on diverse approaches and ongoing advancements, this review aims to foster progress in antiviral therapy for pregnant women, improving maternal and fetal health outcomes.

BACKGROUND: Hepatitis C is a global health burden with significant morbidity and mortality. It primarily affects the liver and causes acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Common modes of transmission of hepatitis C virus (HCV) infection are blood transfusion, needlestick injury, and mother-fetus transmission, among which transmission, blood transfusion is one of the most important causes. Blood transfusion is one of the pillars in the management of patients that saves lives and improves morbidity. Blood donation in India is done by voluntary and replacement blood donors of both sexes. The aim of this study is to determine the seroprevalence of HCV among blood donors in the Jharkhand state, a tribal-preponderant region of India, and to see the trend over the years.
METHODS: This is a nine-year retrospective observational study from 2015 to 2023 that screened for anti-HCV antibodies (third-generation kit: Abbott Diagnostics) using the chemiluminescence technique.
RESULTS: In this study, in total, 249,461 units of blood were collected, of which the majority of donations were by male and replacement donors (RDs) comprising 230,757 (92.50%) and 188,047 (75.38%), respectively. The mean number of blood donations by replacement and male donors (MDs) was more than for voluntary donors (VDs) and female donors (FDs) (20894.11 ± 3041.71 RDs vs. 6823.77 ± 2332.96 VDs, p < 0.0001 and 25639.66 ± 2810.08 MDs vs. 2078.22 ± 828.16 FD, p < 0.0001), respectively. The overall prevalence of HCV was 0.63%, and all seropositive donors were male.
CONCLUSIONS: Replacement blood donation contributes to the major part of blood donation and is primarily done by males in this tribal population-dominant region of India. Seroprevalence of HCV is high in the population of this part of India, and there is a constant or slightly upward trend in hepatitis C infection among individuals.

The association between chronic HCV infection and type 2 diabetes mellitus (T2DM) has been established; however, there is limited research on β-cell function particularly in the pre-diabetic population. Here, we evaluated indices of β-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DM in individuals with and without chronic hepatitis C (CHC), and the effects of antiviral treatments on these variables. A total of 153 non-cirrhotic, non-fibrotic CHC patients with a BMI <25 were enrolled in the study. Among them, 119 were successfully treated with either direct acting antiviral (DAA) drugs or pegylated interferon/ribavirin (IFN/RBV) anti-HCV therapy. Fasting state- and oral glucose tolerance test (OGTT)-derived indexes were used to evaluate β-cell function and insulin sensitivity. Among all subjects, 19 (13%) had T2DM and 21% exhibited pre-diabetes including 8% isolated impaired fasting glucose (IFG) and 13% combined IFG and impaired glucose tolerance (IGT). Early and total insulin secretion adjusted for the degree of insulin resistance were decreased in pre-diabetic CHC patients compared to HCV-uninfected individuals. Viral eradication through DAA or IFN/RBV therapy demonstrated positive impacts on insulin sensitivity and β-cell function in CHC patients who achieved sustained virologic response (SVR), regardless of fasting or OGTT state. These findings emphasize the role of HCV in the development of β-cell dysfunction, while also suggesting that viral eradication can improve insulin secretion, reverse insulin resistance, and ameliorate glycemic control. These results have important implications for managing pre-diabetic CHC patients and could prevent diabetes-related clinical manifestations and complications.

BACKGROUND: There is limited empirical work assessing the effectiveness of treatment as prevention (TasP) in reducing HCV prevalence among people who inject drugs (PWID). Here, we used survey data from the UK during 2010-2020, to evaluate the impact of direct-acting antiviral agent (DAA) treatment scale-up, which started in 2015, on HCV prevalence among PWID.
METHODS: We fitted a logistic regression to time/location specific data on prevalence from the Needle Exchange Surveillance Initiative in Scotland and Unlinked Anonymous Monitoring programme in England. For each post-intervention year and location, we quantified the effect of TasP as the difference between estimated prevalence and its counterfactual (prevalence in the absence of scale-up). Progress to elimination was assessed by comparing most recent prevalence against one in 2015.
RESULTS: In 2015, prevalence ranged from 0.44 to 0.71 across the 23 locations (3 Scottish, 20 English). Compared to counterfactuals, there was an absolute reduction of 46% (95% credible interval [32%,59%]) in Tayside in 2020, 35% ([24%,44%]) in Glasgow in 2019, and 25% ([10%,39%]) in the Rest of Scotland in 2020. The English sites with highest estimated absolute reductions in 2021 were South Yorkshire (45%, [29%,58%]), Thames Valley (49%, [34%,59%]) and West London (41%, [14%,59%]). Compared to 2015, there was 80% probability that prevalence had fallen by 65% in Tayside, 53% in Glasgow and 36% in the Rest of Scotland. The English sites with highest % prevalence decrease compared to 2015, achieved with probability 80%, were Chesire & Merseyside (70%), South Yorkshire (65%) and Thames Valley (71%). Higher treatment intensity was associated with higher reductions in prevalence.
CONCLUSIONS: Conclusion. Real-world evidence showing substantial reductions in chronic HCV associated with increase of HCV treatment scale-up in the community thus supporting the effectiveness of HCV treatmen as prevention in people who inject drugs.

UNASSIGNED: Many individuals living with hepatitis C virus (HCV) are unaware of their diagnosis and/or have not been linked to programs providing HCV care. The use of electronic medical record (EMR) systems may assist with HCV infection identification and linkage to care.
UNASSIGNED: In October 2021, we implemented HCV serology-focused best practice alerts (BPAs) at The Ottawa Hospital (TOH) via our EMR (EPIC). Our BPAs were programmed to identify previously tested HCV seropositive individuals. Physicians were prompted to conduct HCV RNA testing and submit consultation requests to the TOH Viral Hepatitis Program. We evaluated data post-BPA implementation to assess the design and related outcomes.
UNASSIGNED: From 1 September 2022 to 15 December 2022, a total of 2,029 BPAs were triggered for 139 individuals. As a consequence of the BPA prompts, nine HCV seropositive and nine HCV RNA-positive individuals were linked to care. The proportion of total consultations coming from TOH physicians increased post-BPA implementation. The BPA alerts were frequently declined, and physician engagement with our BPAs varied across specialty groups. Programming issues led to unnecessary BPA prompts (e.g., no hard stop to the prompts even though the individual was treated and cured and individuals linked to care without first undergoing HCV RNA testing). A fixed 6-month lookback period for test results limited our ability to identify many individuals.
UNASSIGNED: An EMR-based BPA can assist with the identification and engagement of HCV-infected individuals in care. However, challenges including issues with programming, time commitment toward BPA configuration, productive communication between healthcare providers and the programming team, and physician responsiveness to the BPAs require attention to optimize the impact of BPAs.